Depression after coronary artery bypass graft (CABG) surgery is common (up to 40%) and increases risk of cardiac morbidity and mortality in the first year by more than two fold. However, current scarcity of data on etiopathogenesis of post-CABG depression hampers development of prevention or treatment strategies of post-CABG depression. Vascular Depression hypothesis posits that cerebrovascular disease predisposes, precipitates, or perpetuates late-onset depression and implicates etiopathogenesis and treatment strategies that are different from idiopathic, early-onset depression. Conspicuous similarities in demographics, longitudinal course, and presence of vascular risk factors exist between post-CABG depression and vascular depression. In this revised application this new R01 investigator proposes a prospective cohort study that utilizes Transcranial Doppler ultrasound (TCD) to detect and quantify the location and severity of Intracranial Atherosclerosis (ICA), as well as to assess for other putative pre-CABG risk factors (e.g. pre-CABG depression, neuroticism, low social and support) for post-CABG depression in 200 CABG surgery patients at the time of cardiac catheterization. We will then follow the subjects over the subsequent 12 months to assess for incidence, symptomatology and course of post-CABG depression. We predict that pre-operative burden of ICA, as assessed by TCD, will be a strong independent risk factor for post-CABG depression, and that features and symptomatology (e.g. late age of onset, executive dysfunction, functional impairment, apathy and anhedonia) will be consistent with the Vascular Depression Hypothesis. Confirming these predictions will support the hypothesis that post-CABG depression is a form of Vascular Depression, thus laying the foundation for risk stratification with a mobile, bedside tool and development of etiologically-based prevention strategies to reduce morbidity and mortality associated with post-CABG depression. PUBLIC HEALTH RELEVANCE: Depression after coronary artery bypass graft (CABG) surgery is a significant public health problem with serious consequences for patients and caregivers. Prevention and early diagnosis of depression after CABG surgery is a major priority in managing patients. Testing the Vascular Depression hypothesis and identifying reliable risk factors for post-CABG depression could lay the foundation for the development of etiologically-based risk stratification and prevention strategies to reduce morbidity and mortality associated with post-CABG depression.